1. Technical Field of the Invention
The present invention relates to a pharmaceutical composition comprising an effective amount of an extract or lyophilized extract or at least one bioactive fraction obtained from plant Woodfordia fruticosa along with one or more pharmaceutically acceptable additives/carriers. The present invention particularly provides a composition for treating ulcer caused by the conditions caused by stress induced ulcer, peptic ulcer, cold restraint induced ulcer, drug induced ulcer and acid induced ulcer and also the composition is used as specific inhibitor of gastric H+, K+-ATPase.
2. Background and Prior Art References
Traditional herbal preparations are known for centuries to protect against peptic ulcer diseases, the aetiopathological basis of which were not known in those periods. Current day knowledge about the underlying biochemical mechanism for most of the gastric ulcers and majority of the duodenal ulcers deserve appropriate consideration and due weightage while consolidating the claim regarding the efficacy of a plant extract.
In a Program on ‘Discovery, Development & Commercialization of New Bioactive & Traditional Preparations’, coordinated by Council of Scientific Research, the Applicant has been collecting, extracting and screening different potential plants and their parts for their bioefficacy against various diseases. Gastric ulcer is one such disease. Based on screening through appropriate experimental model(s), the applicant has selected a plant flower as our target for the development of an effective anti ulcer medicine. This invention envisages to claim the potential of an extract obtained from the flower of Woodfordia fruticosa to act as an effective therapy against peptic ulcer diseases.
Reported Medicinal Use:
The plant Woodfordia fruticosa Kurz. Syn. W. floribunda Salisb popularly known in regional languages as “Dhatki” is a much branched shrub with fluted stems and long, spreading branches, grows to a maximum height of 7 m, and occurs throughout North India, ascending to an altitude of about 1,500 m in the Himalayas [Chadha, Y. R. (ed.), The Wealth of India, Raw Materials, Vol. X (1976), Council of Scientific & Industrial Research, New Delhi, pp 586-687]. It is sometimes cultivated in gardens for its flowers. The plant bears numerous flowers, brilliant red in dense axillary paniculate-cymose clusters. The flowers yield a red dye and are employed throughout India for dying fabrics.
The medicinal values of the plant and its parts indicate that the leaves of Woodfordia fruticosa possess antibiotic activity in vitro against Micrococcus pyogens var. aureus as well as sedative properties [Dhar, M. L., Dhar, M. M., Dhawan, B. N., Mehrotra, B. N. and Ray, C., Ind. J. exp. Biol. 6, 232 (1968); Paris, R. R. and Jacquemin, H., Fitoterapia, 47, 51 (1976); Kadota, S., Takamori, Y., Kikuchi, T., Motegi, A. and Ekimoto, H., Chem. Pharm. Bull. 38, 2687 (1990)], and are reported to be used as a folk medicine in India and Nepal. Methanol and water extracts of the leaves of this plant inhibits DNA topoisomerase II [Chen, G. L. and Liu, L. F. Annu. Rep. Medicinal Chemistry, 21, 257 (1986].
A preparation consisting of dried fruits, flowers, buds and broken pieces of inflorescences are commercially used in the management of bowel complaints, haemorrhages, menorrhagia and seminal weakness. An extract of the whole plant was found to stimulate the contraction of the intestinal loop, show antipyretic action [Chadha, Y. R. (ed.), The Wealth of India, Raw Materials, Vol. X (1976), Council of Scientific & Industrial Research, New Delhi, pp 586-687].
The dried flower of this plant are reported to be used for the treatment of haemorrhoids, dysentery, and liver diseases [[Chadha, Y. R. (ed.), The Wealth of India, Raw Materials, Vol. X (1976), Council of Scientific & Industrial Research, New Delhi, pp 586-687; Dhar, M. L., Dhar, M. M., Dhawan, B. N., Mehrotra, B. N. and Ray, C., Ind. J. exp. Biol. 6, 232 (1968); Kirtikar, K. R. and Basu, B. D., Indian Medicinal Plants (Eds. Blatter, E., Caius, J. F. and Mhaskar, K. S.), Vol. II, Publishers: Lalit Mohan Basu, Allahabad, India (1935), p. 1074].
The dried flowers are also credited with stimulant and astringent properties. They are often added to the Ayurvedic Arishtas to cause alcoholic fermentation. Powdered dried flowers when sprinkled over ulcers and wounds, diminish discharge and promote granulation. A paste of the flower is reported to be used for the treatment of coughs. An ointment containing this flower was also used in the pustules of smallpox. An extract of the flowers shows activity against Helminthosporium sativum [Chadha, Y. R. (ed.), The Wealth of India, Raw Materials, Vol. X (1976), Council of Scientific & Industrial Research, New Delhi, pp 586-687; Kirtikar, K. R. and Basu, B. D., Indian Medicinal Plants (Eds. Blatter, E., Caius, J. F. and Mhaskar, K. S.), Vol. II, Publishers: Lalit Mohan Basu, Allahabad, India (1935), p. 1074]. The flowers are reported to be gathered and sucked by children for sweet nectar. They are believed to be eaten, in Madhya Pradesh, and in West Bengal are employed for making a cooling drink [Bhargava, J. Bombay nat. Hist. Soc., 56, 26 (1959); Desai et al. Indian J, Chem. 9, 611 (1971)].
Strategy & Approach Plan:
The concept of management of peptic ulcer diseases is fast changing. Traditionally, treatment was based on the principle that excessive secretion of acid was the sole cause of ulcer symptoms. Later on, a proposed role of psychological stress also gained wide acceptance. Ulcer formation is currently viewed as an interactive process that results from an imbalance of ‘aggressive factors’ like acid, pepsin, smoking, alcohol, pain killer etc. and ‘defensive factors’ like mucin, bicarbonate, milk etc. [Hirschowitz, B. L., Keeling, D., Lewin, M., Okabe, S., Parsons, M., Sewing, K. Wallmark, B. and Sachs, G., Dig. Dis. Sci., 40, 3S (1995)].
It was established in the first quarter of the last century that gastric acid is secreted by a class of gastric cells called parietal cells while the physiological basis of obligatory requirements of K+ and Ca2+ in gastric HCl secretion and regulation came into our knowledge-base in the middle of twentieth century [Modlin, I. M., Surg. Gyneol. Obstet., 170, 81 (1990).
The role of histamine, gastrin and acetylcholine in controlling gastric acid secretion was understood only around the third quarter of last century and this triggered the designing of chemical molecules acting as blockers of such receptors giving rise to functionally effective anti-ulcer drugs [Prinz. C., Kajimura, M., Scott, D., Helander, H., Shin, J., Besancon, M., Bamberg, K., Hersey, S. and Sachs, G., Yale J. Biol. Med. 65, 577 (1992)].
That an enzyme known as ‘Gastric Proton Pump’ is the final common mediator of HCl transport in the stomach lumen was accepted only in 1980s, paving the way for the advent of omeprazole era [Sachs, G., Ann. Rev. Pharmacol. Toxicol, 28, 269 (1998). Finally around 1990s, a bacterium called Helicobacter pylori was shown to be responsible for peptic ulcer and perhaps gastric carcinoma [Adrian Lee and Francis Megraud (eds) Helicobacter pylori: techniques for clinical diagnosis & basic research, W. B. Saunders Company Ltd. 1996].
All these discoveries are being given appropriate consideration in delineating the claim about the efficacy of this single herbal extract. The applicant anticipates bringing in a new generation of herbal medicine in the horizon. Since sufficient tools and knowledge are available today to come very close to identifying the site of action of any unknown principle(s) with a specific mechanism, and since it is imperative that the specific site of action of a new drug be shown before it can be accepted, the applicant has carefully selected four experimental models so as to cover majority of the aetiological factors responsible for the pathogenesis of peptic ulcer diseases.
Objects of the Invention
The main object of the invention is to provide a pharmaceutical composition for treating peptic ulcer and related ulcerical conditions.
Another object of the invention is to provide a pharmaceutical composition comprising lyophilized extract or bioactive fractions obtained from plant Woodfordia fruticosa for the treatment of peptic ulcer caused by various conditions.
Still another object of the present invention is to provide a method of treating ulcers caused by the conditions selected from stress induced ulcer, peptic ulcer, cold restraint induced ulcer, drug induced ulcer and acid induced ulcer.
Yet another object of the invention is using the composition for inhibiting gastric H+, K+-ATPase activity.
Still another object of the invention is to provide a process for preparing lyophilized and bioactive fractions from the flowers of plant Woodfordia fruticosa. 